In this week’s episode we discuss encouraging results of a phase 2 study using a sequential ibrutinib-venetoclax treatment approach driven by MRD findings in individual patients with chronic lymphocytic leukemia, or CLL. Next, we examine new research demonstrating that donor natural killer cells trigger release of beta-2 microglobulin by host dendritic cells, greatly accelerating donor-derived immune reconstitution after allogeneic bone marrow transplant in mice. We’ll look at the therapeutic implications of this as well. Lastly, we review a study of retinoic acid resistance in a mouse model of variant acute promyelocytic leukemia. Resistance was driven by the epigenetic regulator EZH2, which suggests the potential for an EZH2-targeted therapeutic approach.

Using MRD to guide CLL treatment intensity, donor NK cells boost immune reconstitution after haplo-BMT, and  EZH2 drives retinoic acid resistance in variant APL

The Blood Podcast summarizes content recently published in Blood, the most cited peer-reviewed publication in the field of hematology.

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In this week's podcast we'll discuss another step forward in stamping out high-risk myeloma. Then we'll hear about the plasmin-cleaved von Willebrand factor, or VWF, in microthrombosis. Finally we'll hear about new insights into the origins of sickle cell pain.  Featured Articles:Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly
diagnosed myelomaPlasmin-cleaved von Willebrand factor as a biomarker for microvascular thrombosisSickle cell disease iPSC-derived sensory neurons exhibit increased excitability and sensitization to patient
plasma

Stamping out high-risk myeloma with D-KRd and tandem transplant; plasmin-cleaved VWF in microthrombosis; SCD plasma sensitizes iPSC-derived sensory neurons

In this week's episode we’ll discuss the utility of MRD in identifying patients with NPM1 AML who benefit from allogeneic transplant in first remission, learn more about the contribution of circulating hematopoietic stem/progenitor cell subsets to human hematopoietic hemostasis, and discuss the role of Let-7 miRNAs in regulation of BCL11A transcription and hemoglobin switching.  Featured Articles:Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remissionlet-7 miRNAs repress HIC2 to regulate BCL11A transcription and hemoglobin switching Circulating Hematopoietic Stem/Progenitor Cell subsets contribute to human hematopoietic homeostasis


Allogeneic transplant in first remission for post-induction molecular MRD; circulating HSPCs actively participate in human hematopoiesis; let-7 miRNAs repress HIC2 to regulate BCL11A transcription and

In this week's epside we'll learn about ADAMTS recovery after caplacizumab therapy in patients with immune thrombotic thrombocytopenic purpura. Then, we'll hear about preclinical characterization of sonrotoclax, a potential second-generation BCL2 inhibitor. Finally we'll hear about new insights into the etiology of Castleman disease where researchers describe the unusual occurrence of idiopathic multicentric Castleman disease in identical twins.  Featured Articles: ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapySonrotoclax overcomes BCL2 G101V mutation–induced venetoclax resistance in preclinical models of
hematologic malignancySingle-cell landscape of idiopathic multicentric Castleman disease in identical twins

ADAMTS13 recovery in caplacizumab-treated TTP; inhibition of venetoclax-resistant BCL2 variants with sonrotoclax; genomic insights from Castleman disease in twins

In this week's episode, we’ll discuss the findings from a study assessing responses after treatment with tisagenlecleucel [LM1] in adults with relapsed/refractory follicular lymphoma, learn more about the association between high microRNA-145 plasma levels and decreased risk of future incident venous thromboembolism, and discuss how epigenetic and immunogenetic signatures can be used in the prediction of outcomes for high-count monoclonal B lymphocytosis. 
Featured Articles: Durable Response After Tisagenlecleucel in Adults With Relapsed/Refractory Follicular Lymphoma: ELARA Trial Update Prediction of outcomes for high-count monoclonal B lymphocytosis using an epigenetic and immunogenetic signature High microRNA-145 plasma levels are associated with decreased risk of future incident venous thromboembolism: The HUNT study 

Durable response after tisa-cel in adults with relapsed/refractory follicular lymphoma; high microRNA-145 plasma levels indicate decreased risk of VTE; epigenetic/immunogenetic signature in the predic

In this week's episode, we'll discuss gut microbiota exploitation by CPX-351 in acute myeloid leukemia. Then we'll learn about optimizing anti-myeloma immunity. New research shows that regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation. Finally we'll discuss among pediatric patients with ITP or other autoimmune cytopenias, which ones will go on to develop systemic lupus?  Featured Articles: CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance, and immune homeostasisRegulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantationAntinuclear antibody–associated autoimmune cytopenia in childhood is a risk factor for systemic lupus erythematosus

Using MRD to guide CLL treatment intensity, donor NK cells boost immune reconstitution after haplo-BMT, and EZH2 drives retinoic acid resistance in variant APL

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